Toll-like receptor (TLR2 and TLR4) polymorphisms and chronic obstructive pulmonary disease

PLoS One. 2012;7(8):e43124. doi: 10.1371/journal.pone.0043124. Epub 2012 Aug 28.


Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV(1) and sputum inflammatory cells in moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV(1) and accelerated decline of FEV(1) and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs was associated with FEV(1) level. Eleven out of 17 SNPs were associated with FEV(1) decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Gene Expression Regulation*
  • Humans
  • Inflammation
  • Longitudinal Studies
  • Lung / pathology
  • Male
  • Middle Aged
  • Models, Biological
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Sputum / metabolism
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 4 / genetics*


  • Toll-Like Receptor 2
  • Toll-Like Receptor 4

Grants and funding

This work was supported by the Graduate School for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, the Netherlands; The GLUCOLD study was supported by unrestricted grants of the Netherlands Organization for Scientific Research (NWO; 940-35-033), the Netherlands Asthma Foundation (NAF; 37.97.74 and, GlaxoSmithKline (NL), Leiden University Medical Center (LUMC), and University of Groningen (RUG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.